Molecular patterns in the evolution of serrated lesion of the colorectum.

Colorectal cancer (CRC) mostly develops from a variety of polyps following mainly three different molecular pathways: chromosomal instability (CIN), microsatellite instability (MSI) and CpG island methylation (CIMP). Polyps are classified histologically as conventional adenomas, hyperplastic polyps, sessile serrated adenomas/polyps (SSA/P) and traditional serrated adenomas (TSA). However, the association of these polyps with the different types of CRCs and the underlying genetic and epigenetic aberrations has yet to be resolved. In order to address this question we analyzed 140 tumors and 20 matched mucosae by array comparative genomic hybridization, by sequence analysis of the oncogenes BRAF, KRAS, PI3K3CA and by methylation arrays. MSI was tested indirectly by immunohistochemistry (IHC) and a loss of MLH1, MSH2, MSH6 or PMS2 was assigned as high microsatellite instability (MSI-H), while low microsatellite instability (MSI-L) was defined as MGMT IHC negativity only. CIN was detected in 78% of all MSI-H CRCs, most commonly as a gain of chromosome 8. Methylation data analyses allowed classification of samples into four groups and detected similar methylation profiles in SSA/P and MSI-H CRC. TSA also revealed aberrant methylation pattern, but clustered more heterogeneously and closer to microsatellite stable (MSS) CRCs. SSA/P, TSA and MSI-H CRCs had the highest degree of promotor methylation (CIMP pathway). Chromosomal instability, in contrast to the established doctrine, is a common phenomenon in MSI CRCs, yet to a lower extent and at later stages than in MSS CRCs. Methylation analyses suggest that SSA/P are precursors for MSI-H CRCs and follow the CIMP pathway.

Morphological subtypes of colorectal low-grade intraepithelial neoplasia: diagnostic reproducibility, frequency and clinical impact.

AIMS: Special histomorphological subtypes of colorectal low-grade intraepithelial neoplasia (LGIN) with variable prognostic impact were recently described in patients with inflammatory bowel disease (IBD) referred to as non-conventional dysplasia. However, they can also be found in patients without IBD. We aimed to analyse the reproducibility, frequency and prognostic impact of non-conventional colorectal LGIN in patients with and without IBD. METHODS: Six pathologists evaluated 500 specimens of five different LGIN-cohorts from patients with and without IBD. Non-conventional LGIN included hypermucinous, goblet cell-deficient, Paneth cell-rich and crypt cell dysplasia. A goblet cell-rich type and non-conventional LGIN, not otherwise specified were added. Results were compared with the original expert-consented diagnosis from archived pathology records. RESULTS: Four or more pathologists agreed in 86.0% of all cases. Non-conventional LGIN was seen in 44.4%, more frequently in patients with IBD (52%; non-IBD: 39.3%, p=0.005). In patients with IBD non-conventional LGIN associated with more frequent and earlier LGIN relapse (p=0.006, p=0.025), high-grade intraepithelial neoplasia (p=0.003), larger lesion size (p=0.001), non-polypoid lesions (p=0.019) and additional risk factors (p=0.034). Results were highly comparable with expert-consented diagnoses. In patients without IBD, non-conventional LGIN may indicate a higher risk for concurrent or subsequent colorectal carcinoma (CRC, p=0.056 and p=0.061, respectively). Frequencies and association with high-grade intraepithelial neoplasia or CRC varied between the different LGIN subtypes. CONCLUSIONS: Non-conventional histomorphology in colorectal LGIN is frequent and highly reproducible. Our results indicate an increased risk for CRC in patients with non-conventional LGIN, probably independent of IBD. We recommend reporting non-conventional LGIN in routine pathology reports.

[A rare case of renal ectopic thyroid tissue]. / Ein seltener Fall eines renalen ektopen Schilddrüsengewebes.

We present a rare case of ectopic thyroid tissue found during robotic nephrectomy of a kidney with a suspected malignant tumour. Such cases of ectopic thyroid tissue are extremely rare in the literature. If ectopic thyroid tissue occurs, it is usually found in the neck region or in the upper mediastinum. Clinical symptoms depend on size, localisation and hormonal function of the ectopic tissue. Surgical resection remains the treatment of choice; in individual cases, conservative treatment can be an option. This case report aims to emphasise that renal tumours of unknown origin might be paraneoplastic or ectopic tissue of other organs.

MET Amplification in Non-Small Cell Lung Cancer (NSCLC)-A Consecutive Evaluation Using Next-Generation Sequencing (NGS) in a Real-World Setting.

In non-small cell lung cancer (NSCLC), approximately 1-3% of cases harbor an increased gene copy number (GCN) of the MET gene. This alteration can be due to de novo amplification of the MET gene or can represent a secondary resistance mechanism in response to targeted therapies. To date, the gold standard method to evaluate the GCN of MET is fluorescence in situ hybridization (FISH). However, next-generation sequencing (NGS) is becoming more relevant to optimize therapy by revealing the mutational profile of each NSCLC. Using evaluable n = 205 NSCLC cases of a consecutive cohort, this study addressed the question of whether an amplicon based NGS assay can completely replace the FISH method regarding the classification of MET GCN status. Out of the 205 evaluable cases, only n = 9 cases (43.7%) of n = 16 high-level MET amplified cases assessed by FISH were classified as amplified by NGS. Cases harboring a MET GCN > 10 showed the best concordance when comparing FISH versus NGS (80%). This study confirms that an amplicon-based NGS assessment of the MET GCN detects high-level MET amplified cases harboring a MET GCN > 10 but fails to detect the various facets of MET gene amplification in the context of a therapy-induced resistance mechanism.

Selective activation of trophoblast-specific PLAC1 in breast cancer by CCAAT/enhancer-binding protein beta (C/EBPbeta) isoform 2.

The trophoblast-specific gene PLAC1 (placenta-specific 1) is ectopically expressed in a wide range of human malignancies, most frequently in breast cancer, and is essentially involved in cancer cell proliferation, migration, and invasion. Here we show that basal activity of the PLAC1 promoter is selectively controlled by ubiquitous transcription factor SP1 and isoform 2 of CCAAT/enhancer-binding protein beta that we found to be selectively expressed in placental tissue and cancer cells. Binding of both factors to their respective elements within the PLAC1 promoter was essential to attain full promoter activity. Estrogen receptor alpha (ERalpha) signaling further augmented transcription and translation of PLAC1 and most likely accounts for the positive correlation between PLAC1 expression levels and the ERalpha status we observed in primary breast cancer specimens. DNA affinity precipitation and chromatin immunoprecipitation assays revealed that transactivation of the PLAC1 promoter by ligand-activated ERalpha is based on a nonclassical pathway independent of estrogen-response elements, by tethering of ERalpha to DNA-bound CCAAT/enhancer-binding protein beta-2, and SP1. Our findings provide first insight into a novel and hitherto unknown regulatory mechanism governing selective activation of trophoblast-specific gene expression in breast cancer.

Budesonide is effective in treating lymphocytic colitis: a randomized double-blind placebo-controlled study.

BACKGROUND & AIMS: Budesonide is effective in treating collagenous colitis, but no treatment is established for lymphocytic colitis. We performed a randomized, double-blind, placebo-controlled study to evaluate the effects of budesonide in patients with lymphocytic colitis. METHODS: Forty-two patients (median age, 61 years) with lymphocytic colitis and chronic diarrhea were randomly assigned to groups that were given oral doses of budesonide (9 mg/d) or placebo for 6 weeks. Nonresponders at week 6 were given open-label budesonide (9 mg/d) for 6 additional weeks. A complete colonoscopy and histologic and quality-of-life analyses were performed at baseline and at week 6. The primary end point was clinical remission at 6 weeks, with last observation carried forward (LOCF). All patients who left the study in clinical remission were followed for relapse. RESULTS: At week 6, 86% of patients given budesonide were in clinical remission (with LOCF) compared with 48% of patients given placebo (P = .010). Furthermore, open-label budesonide therapy induced clinical remission in 7 of 8 patients given placebo. Histologic remission was observed in 73% of patients given budesonide compared with 31% given placebo (P = .030). Only 1 patient discontinued budesonide therapy prematurely. During a mean follow-up period of 14 months, 15 patients (44.1%) experienced a clinical relapse (after a mean of 2 months); 8 of the relapsing patients were retreated with and responded again to budesonide. CONCLUSIONS: Budesonide effectively induces clinical remission in patients with lymphocytic colitis and significantly improves histology results after 6 weeks. Clinical relapses occur but can be treated again with budesonide.

ERG rearrangement in small cell prostatic and lung cancer.

AIMS: Small cell prostatic cancer is a rare but aggressive disease. Currently, its histogenetic origin is unclear and its distinction from metastatic small cell lung cancer is challenging. The aim of our study was to determine whether the ERG rearrangement commonly observed in acinar prostatic cancer can distinguish small cell prostatic cancer from small cell lung cancer samples. METHODS AND RESULTS: We assessed 15 small cell prostatic cancers and 22 small cell lung cancers for ERG rearrangement using fluorescence in situ hybridization. Commonly used and novel immunohistochemical markers (i.e. androgen receptor, calcium activated nucleotidase 1, Golgi phosphoprotein 2, prostate-specific antigen, prostate-specific membrane antigen, CD56, epithelial membrane antigen, thyroid transcription factor 1, chromogranin A, synaptophysin and Ki67) were further studied. ERG rearrangement occurred in 86% of small cell prostatic cancers but in none of the small cell lung cancers and was the best marker to differentiate between both tumours (P < 0.0001). CONCLUSIONS: The ERG rearrangement is commonly observed in small cell prostatic cancer, supporting the hypothesis that ERG rearrangement occurs in aggressive prostatic cancers. Furthermore, the ERG rearrangement is the most significant marker to differentiate between small cell prostatic cancer and small cell lung cancer. Moreover, our data suggest that small cell prostatic cancer is not a tumour entity on its own, but a dedifferentiated variant of common acinar prostatic cancer.

Sporadic adenoma or ulcerative colitis associated neoplasia? The endoscopist's information has an impact on diagnosis and patient management.

BACKGROUND: Diagnosing low grade intraepithelial neoplasia (LGIN) in patients with ulcerative colitis (UC) is difficult. Distinguishing between sporadic adenoma (SA) and UC associated LGIN is even more challenging but has clinical impact. We aimed to examine, if the morphological distinction between both entities is reliably possible, how it influences patient's outcome and the role of the endoscopist in this decision with respect to current endoscopy classification schemes. METHODS: Seven pathologists retrospectively reevaluated 425 cases of LGIN in UC patients, diagnosed between 2009 and 2017 with preceding expert consensus and follow up in two separate readings, based on published morphological differentiation criteria. In the first evaluation, the observers were blinded to any clinical data. In the second evaluation, they knew patients' age as well as endoscopic features. They also rated their subjective diagnostic certainty. RESULTS: Diagnostic correctness improved significantly in the second assessment as did the pathologists' confidence in their diagnoses (p < 0.001 - p = 0.019). Knowledge of clinical and endoscopical data led to a higher percentage of SA (71.8% vs. 85.6%). UC associated LGIN showed significant earlier LGIN relapse as well as more high grade intraepithelial neoplasia and carcinoma during follow up (p < 0.001, p < 0.001, p = 0.005). CONCLUSIONS: Distinction between SA and UC associated LGIN is important as it has an impact on patients' follow up and treatment. Morphological distinction remains difficult with moderate interobserver variability. Adequate clinical information significantly improves pathologists' diagnoses as well as their confidence in their diagnoses.

Claudin-18 splice variant 2 is a pan-cancer target suitable for therapeutic antibody development.

PURPOSE: Antibody-based cancer therapies have emerged as the most promising therapeutics in oncology. The purpose of this study was to discover novel targets for therapeutic antibodies in solid cancer. EXPERIMENTAL DESIGN: We combined data mining and wet-bench experiments to identify strictly gastrocyte lineage-specific cell surface molecules and to validate them as therapeutic antibody targets. RESULTS: We identified isoform 2 of the tight junction molecule claudin-18 (CLDN18.2) as a highly selective cell lineage marker. Its expression in normal tissues is strictly confined to differentiated epithelial cells of the gastric mucosa, but it is absent from the gastric stem cell zone. CLDN18.2 is retained on malignant transformation and is expressed in a significant proportion of primary gastric cancers and the metastases thereof. In addition to its orthotopic expression, we found frequent ectopic activation of CLDN18.2 in pancreatic, esophageal, ovarian, and lung tumors, correlating with distinct histologic subtypes. The activation of CLDN18.2 depends on the binding of the transcription factor cyclic AMP-responsive element binding protein to its unmethylated consensus site. Most importantly, we were able to raise monoclonal antibodies that bind to CLDN18.2 but not to its lung-specific splice variant and recognize the antigen on the surface of cancer cells. CONCLUSIONS: Its highly restricted expression pattern in normal tissues, its frequent ectopic activation in a diversity of human cancers, and the ability to specifically target this molecule at the cell surface of tumor cells qualify CLDN18.2 as a novel, highly attractive pan-cancer target for the antibody therapy of epithelial tumors.

A placenta-specific gene ectopically activated in many human cancers is essentially involved in malignant cell processes.

The identification and functional characterization of tumor-specific genes is a prerequisite for the development of targeted cancer therapies. Using an integrated data mining and experimental validation approach for the discovery of new targets for antibody therapy of cancer, we identified PLAC1. PLAC1 is a placenta-specific gene with no detectable expression in any other normal human tissue. However, it is frequently aberrantly activated and highly expressed in a variety of tumor types, in particular breast cancer. RNAi-mediated silencing of PLAC1 in MCF-7 and BT-549 breast cancer cells profoundly impairs motility, migration, and invasion and induces a G1-S cell cycle block with nearly complete abrogation of proliferation. Knockdown of PLAC1 is associated with decreased expression of cyclin D1 and reduced phosphorylation of AKT kinase. Moreover, PLAC1 is localized on the surface of cancer cells and is accessible for antibodies which antagonize biological functions of this molecule. These features, in summary, make PLAC1 an attractive candidate for targeted immunotherapeutic approaches.

In silico strategy for detection of target candidates for antibody therapy of solid tumors.

In contrast to earlier attempts for the identification of target candidates suitable for monoclonal antibody (mAb) based cancer therapies we concentrated on highly selective lineage-specific genes additionally preserved or even overexpressed in orthotopic cancers. In a script aided workflow we reduced all human entries of the RefSeq mRNA database to those encoding transmembrane domain bearing gene products and subjected them to BLAST analysis against the human EST database. All BLAST results were validated in a gene centric way allowing two types of data curation prior to expression profiling of matching ESTs in selected healthy tissues: (i) exclusion of questionable ESTs arising e.g. from genomic contamination and (ii) elimination of erroneously predicted mRNAs as well as transcripts with only weak EST coverage. The impact of such stringent input control on accuracy of prediction is underlined by RT-PCR confirmation of predicted tissue distribution patterns for a number of selected candidates.

Multiple splice variants of lactate dehydrogenase C selectively expressed in human cancer.

We applied a combined data mining and experimental validation Approach for the discovery of germ cell-specific genes aberrantly expressed in cancer. Six of 21 genes with confirmed germ cell specificity were detected in tumors, indicating that ectopic activation of testis-specific genes in cancer is a frequent phenomenon. Most surprisingly one of the genes represented lactate dehydrogenase C (LDHC), the germ cell-specific member of the lactate dehydrogenase family. LDHC escapes from transcriptional repression, resulting in significant expression levels in virtually all tumor types tested. Moreover, we discovered aberrant splicing of LDHC restricted to cancer cells, resulting in four novel tumor-specific variants displaying structural alterations of the catalytic domain. Expression of LDHC in tumors is neither mediated by gene promotor demethylation, as previously described for other germ cell-specific genes activated in cancer, nor induced by hypoxia as demonstrated for enzymes of the glycolytic pathway. LDHC represents the first lactate dehydrogenase isoform with restriction to tumor cells. In contrast to other LDH isoenzymes, LDHC has a preference for lactate as a substrate. Thus LDHC activation in cancer may provide a metabolic rescue pathway in tumor cells by exploiting lactate for ATP delivery.

Frequent nonrandom activation of germ-line genes in human cancer.

The growing class of cancer/germ-line genes is characterized by a unique expression pattern with transcription restricted to germ cells and cancer cells. It is not known which fraction of germ-line genes is ectopically activated in tumor cells and whether this fraction displays common features as compared with strictly germ-line genes remaining silent in cancer. Using an unbiased genome-wide scanning approach, representative samples of both cancer/germ-line genes as well as strictly germ-line-specific genes were determined. Comparative analysis disclosed highly significant diametric characteristics for these two categories of genes with regard to sex specificity, developmental stage of physiological expression during gametogenesis, chromosomal localization, and epigenetic regulation of expression. Our findings provide class predictors for germ cell-specific gene activation in cancer. The identification of highly congruent expression patterns in cancer and in DNA methyltransferase-deficient cells suggests an underlying common epigenetic mechanism for activation of germ-line genes in cancer.

An international study comparing conventional versus mRNA level testing (TargetPrint) for ER, PR, and HER2 status of breast cancer.

To compare results from messenger RNA (mRNA)-based TargetPrint testing with those from immunohistochemistry (IHC) and in situ hybridization (ISH) conducted according to local standard procedures at hospitals worldwide. Tumor samples were prospectively obtained from 806 patients at 22 hospitals. The mRNA level of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) was assessed by TargetPrint quantitative gene expression readouts. IHC/ISH assessments were performed according to local standards at the participating hospitals. TargetPrint readout showed a high concordance with IHC/ISH of 95 % (kappa 0.81) for ER, 81 % (kappa 0.56) for PR, and 94 % (kappa 0.76) for HER2. The positive/negative agreement between TargetPrint and IHC for ER, PR, and HER2 was 96 %/87 %, 84 %/74 %, and 74 %/98 %, respectively. The concordance rate in IHC/ISH results between hospitals varied: 88-100 % for ER (kappa 0.50-1.00); 50-100 % for PR (kappa 0.20-1.00); and 90-100 % for HER2 (kappa 0.59-1.00). mRNA readout of ER, PR, and HER2 status by TargetPrint was largely comparable to local IHC/ISH analysis. However, there was substantial discordance in IHC/ISH results between different hospitals. When results are discordant, the use of TargetPrint would improve the reliability of hormone receptor and HER2 results by prompting retesting in a reference laboratory.

Intraductal carcinoma of prostate reporting practice: a survey of expert European uropathologists.

BACKGROUND: It is unclear whether the reported variation in the diagnosis of intraductal carcinoma of the prostate (IDC-P) is due to variable interpretation of borderline morphology, use of different diagnostic criteria or both. AIMS: We sought to determine the degree of variation in the diagnostic criteria and reporting rules for IDC-P in prostate biopsies employed by expert uropathologists. METHODS: A questionnaire survey was circulated to 23 expert uropathologists from 11 European countries. RESULTS: Criteria used for diagnosis of IDC-P included solid intraductal growth (100%), dense cribriform (96%), loose cribriform/micropapillary with nuclear size >6× normal (83%) or comedonecrosis (74%) and dilated ducts >2× normal (39%). 'Nuclear size' was interpreted as nuclear area by 74% and nuclear diameter by 21%. Pure IDC-P in needle biopsies was reported by 100% and Gleason graded by 30%. All would perform immunohistochemistry in such cases to rule out invasive cancer. An IDC-P component associated with invasive cancer would be included in the determination of tumour extent and number of cores involved by 74% and 83%, respectively. 52% would include IDC-P component when grading invasive cancer. 48% would perform immunohistochemistry in solid or cribriform nests with comedonecrosis to exclude IDC-P (17% routinely, 30% if the focus appeared to have basal cells on H&E). 48% graded such foci as Gleason pattern 5 even if immunohistochemistry demonstrated the presence of basal cells. CONCLUSIONS: There is a need for more clarity in the definition of some of the diagnostic criteria for IDC-P as well as for greater standardisation of IDC-P reporting.

A novel tumour associated leucine zipper protein targeting to sites of gene transcription and splicing.

We describe here the definition and characterization of antigen CT-8/HOM-TES-85 encoded by a previously unknown gene and identified by serological expression screening using antibodies from a seminoma patient. Intriguingly, the leucine zipper region of CT-8/HOM-TES-85 shows an atypical amphipathy with clusters of hydrophobic residues that is exclusively shared by the N-myc proto-oncogene. CT-8/HOM-TES-85 gene is tightly silenced in normal tissues except for testis. However, it is frequently activated in human neoplasms of different types including lung cancer, ovarian cancer, melanoma and glioma. Endogenous as well as heterogeneously expressed CT-8/HOM-TES-85 targets predominantly to the nucleus forming a distinctive speckled pattern of nuclear dots arranged in macromolecular structures. By co-localization studies these speckles were identified as loci of transcriptional activity and splicing, suggesting that CT-8/HOM-TES-85 may be involved in these processes. The aberrant expression of CT-8/HOM-TES-85 in human neoplasms might therefore be involved in cancer associated alterations of transcriptional or post-transcriptional processes and thus may disclose new mechanisms involved in the manifestation of the cancer phenotype.

Computational dissection of tissue contamination for identification of colon cancer-specific expression profiles.

Microarray profiles of bulk tumor tissues reflect gene expression corresponding to malignant cells as well as to many different types of contaminating normal cells. In this report, we assess the feasibility of querying baseline multitissue transcriptome databases to dissect disease-specific genes. Using colon cancer as a model tumor, we show that the application of Boolean operators (AND, OR, BUTNOT) for database searches leads to genes with expression patterns of interest. The BUTNOT operator for example allows the assignment of "expression signatures" to normal tissue specimens. These expression signatures were then used to computationally identify contaminating cells within conventionally dissected tissue specimens. The combination of several logic operators together with an expression database based on multiple human tissue specimens can resolve the problem of tissue contamination, revealing novel cancer-specific gene expression. Several markers, previously not known to be colon cancer associated, are provided.

The pro-apoptotic FAS-associated factor 1 is specifically reduced in human gastric carcinomas.

The Fas-associated factor 1, FAF1, is a protein, which was first identified as an interaction partner of the death receptor Fas. Not much is known about the function of FAF1, but it has been found that it is able to potentiate Fas-induced apoptosis in cell lines. To clarify the role of FAF1 in human cancer, a number of tumors from different organs were screened for expression of the protein, and it was only found reduced in gastric carcinoma tissue. Thus, 58 human gastric carcinomas were collected, and the expression of FAF1 was analyzed by Western blotting and in a few cases also by immunohistochemistry. The hypothesis was that since FAF1 is able to potentiate apoptosis, it would likely be reduced in the gastric carcinomas in order for them to escape apoptosis. We found that FAF1 was reduced in 50% (29/58) of the gastric carcinomas analyzed as compared to non-neoplastic gastric mucosa from the same patients. 26 of the investigated carcinomas contained signet ring cells, and FAF1 was significantly reduced in 69% of these (p=0.017), whereas it was only reduced in 34% of the carcinomas without signet ring cells. The observed reduction of FAF1 was predominantly caused by proteolytic cleavage of the protein. Additionally, 31 colorectal carcinomas were analyzed for expression of FAF1. Here, FAF1 was only reduced in 16% of the carcinomas when compared to non-neoplastic colorectal mucosa. Our findings support the hypothesis that FAF1 is reduced in gastric carcinomas compared to non-neoplastic tissue, and there was a significant relation between FAF1 reduction and content of signet ring cells in the gastric carcinomas. Also, the reduction of FAF1 is likely to be specific for gastric cancer, which might be due to the fact that signet ring cells are most frequently found in gastric cancers.

Assessing optimal promoter activity for constructs in gastrointestinal gene therapy.

BACKGROUND: During recent decades, studies of various cancer-related genes has led to a growing understanding of molecular mechanisms of gastrointestinal cancer resulting in a genetic progression model. Nevertheless, with a few exceptions, our knowledge of participating genes has not been exploited for gene therapeutic approaches. Therefore, we monitored the promoter activity of genes shown to be significantly expressed in gastrointestinal tumors to select optimally active promoters for recombinant DNA constructs. Such molecules will contain a suicide gene under a suitable cell type-specific regulatory element. MATERIALS AND METHODS: Using promoter-reporter gene (luciferase) constructs we compared the activities of KRT19, TFF1, SEL1L, MUC4, MUC1, CEL and hTERT by transfecting them into the gastrointestinal cell lines MKN45 and DAN-G for transient expression. Furthermore we tested the endogenous expression of these genes by RT-PCR. RESULTS: From a selection of 9 promoter constructs SEL1L, KRT19 and MUC1 displayed the highest activity levels while others were moderately expressed. CONCLUSION: These three appear the most capable ones to drive suicide genes, like thymidine kinase or cytosine deaminase, a study presently initiated.

Promoter selection for the cytosine deaminase suicide gene constructs in gastric cancer.

OBJECTIVE: Carcinomas of the digestive tract represent the second most abundant type of carcinomas in the Western world. During the past two decades, studies of genetic alterations in oncogenes, tumor-suppressor genes, and further cancer-related genes led to growing understanding of molecular mechanisms of gastrointestinal cancer resulting in a genetic progression model. Nevertheless, with a few exceptions, our knowledge of participating genes has not been exploited for gene therapy approaches. Therefore, we monitored promoter activity of a variety of genes shown to be significantly expressed in gastric tumor cells to select optimally active promoters for therapeutical recombinant DNA constructs. When driving a suicide gene these genetic elements can exert cytotoxic effects. METHODS: Using promoter-reporter gene (luciferase) constructs we compared the activities of KRT19, TFF1, SEL1L, MUC4, MUC1, CEL and hTERT by transfecting them into the gastrointestinal cell lines MKN45 and DAN-G for transient expression. After choosing strong promoters we tested the expression of the prokaryotic cytosine deaminase and its cytotoxic effect on the cell cultures. RESULTS: The promoters of SEL1L, MUC1 and KRT19 displayed the highest activity levels in reporter gene assays while other genes reported as upregulated in gastric cancer were moderately expressed. When driving cytosine deaminase in MKN45 cells, the SEL1L promoter induced a 66% cytotoxic effect and the TP1 promoter reached 82%. CONCLUSIONS: From a selection of nine promoter constructs three proved to upregulate the reporter gene well above the level of average activity. They also appear highly capable to drive a suicide gene construct, here tested using prokaryotic cytosine deaminase.